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Fig. 4 | BMC Cancer

Fig. 4

From: System-based approaches as prognostic tools for glioblastoma

Fig. 4

APOPTO-CELL can conduct in silico clinical trials for targeted apoptosis sensitization with SMAC mimetics. a-c Patient-specific dose-response curves simulated by APOPTO-CELL depicting the relationship between apoptosis susceptibility and pharmacological intervention. Apoptosis susceptibility is represented by the amount of simulated substrate cleavage reached at 15 min from the simulation start. Left hand-side of each plot before gap highlights basal apoptosis susceptibility (i.e. no administration of SMAC mimetics). Concentrations of SMAC mimetics tested in silico where selected to span the physiological doses administered in real-world clinical trials (1 nM - 1 μM). Patients were deemed “responsive to standard therapy” if classified as apoptosis-sensitive in simulations without any SMAC mimetics intervention (n = 37, a). Conversely, patients predicted to have apoptosis impairment in basal settings were deemed “responsive to only standard therapy and SMAC mimetics” (n = 3, b) or “non-responsive to standard therapy and SMAC mimetics” (n = 6, c) if administration of SMAC mimetics could induce (or not) re-sensitization, respectively

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